Several prior art processes are known for preparing benzylpyruvates and derivatives thereof, but these processes either result in low product yields, require the use of uneconomical reagents, involve extensive processing steps, or present environmental and safety concerns.
For example, M. Kie, et. al., [Yiyao Gongye, 17(3), 99-101 (1988)] disclose a process where the benzylpyruvic condensation product is subjected to hydride reduction which results in reducing both the olefinic bond and the ketone function. This requires that the .alpha.-hydroxy group be oxidized in order to regenerate the ketone. In this process, it is the saturated .alpha.-keto acids that are subjected to esterification.
R. Barner, et. al., [U.S. Pat. No. 4,675,421 (1988)] disclose the preparation of hydroquinone derivatives used to produce d-.alpha.-tocophenol and the preparation of various hydroquinone starting materials. Several examples disclose processes for preparing 4-aryl-2-ketobutanoic acids and esters by sequentially condensing substituted aryl aldehydes with pyruvic acid, catalytically reducing the .beta.,.gamma.-unsaturated-.alpha.-keto acid salts with a Pd/C catalyst in an aqueous base and esterifying the reduction product with N,N'-carbonyldiimidazole (CDI) and a complex alcohol.
In the processes disclosed by R. Barner, et. al., for preparing the ketobutanoic acids and esters, the condensation reaction is run in alcoholic KOH at reflux temperatures thereby limiting the processes to aryl aldehydes which are deactivated by substitution with alkoxy and alkyl groups. In addition, the esterification steps utilize only saturated .alpha.-keto acids which require the use of relatively costly coupling agents (e.g., CDI) to achieve good yields. The use of costly coupling agents may be justified when coupling equally costly alcohols and acids, but they become uneconomical when lower alkyl compounds are prepared such as those of the present invention.
M. Reimer [J. Am. Chem. Soc. 46 (1924)] discloses a process for synthesizing methyl and ethyl benzalpyruvate by condensing pyruvic acid and benzalaldehyde in water in the presence of sodium hydroxide; isolating and drying the sodium salt of benzalpyruvic acid; redissolving and reprecipitating the salt as the free acid; and, esterifying the thusly isolated acid by conventional Fisher esterification. The .beta.,.gamma.-unsaturated-.alpha.-keto ester product was obtained in low yields and low purity.